Insulin Analogs or Premixed Insulin Analogs in Combination With Oral Agents for Treatment of Type 2 Diabetes

Philip Levy, MD, FACE


April 16, 2007

Newer Therapies for Diabetes Management

Newer agents with novel mechanisms of action are available or in development. Exenatide, for example, is a subcutaneously injected incretin mimetic that enhances glucose-dependent insulin secretion. Recent clinical trial results have indicated that exenatide administration near mealtimes can reduce PPG.65 In published trials, the reduction in A1C observed in patients treated with exenatide is modest, approximately 1%. One distinct benefit with exenatide, however, is its effect on body weight, with patients reporting weight reductions of 1.6-2.8 kg over 30 weeks.[66] Dipeptidyl peptidase-IV (DPP-IV) is an enzyme that inactivates incretins (ie, glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide-1 [GLP-1]) that have antidiabetic actions.[67] Blockade of this enzyme with oral DPP-IV inhibitors is another therapeutic strategy.[68] The first DPP-IV inhibitor, sitagliptin, has recently been approved in the United States for treatment of patients with type 2 diabetes. Addition of another DPP-IV inhibitor, vildagliptin, to metformin decreased A1C by 0.5% to 1.1% without weight gain.[69] A recent review gives more comprehensive information on these emerging therapies.[70] Due to their lower overall glucose-lowering activity, limited clinical data, and relative expense, these agents were not included in the recently published ADA/EASD algorithm.[11]

Inhaled RHI is also now available. When compared with subcutaneous RHI, inhaled insulin has a more rapid onset of action. However, the length of time that inhaled insulin and RHI persist in the circulation are similar.[71] In combination with basal insulin, inhaled insulin has shown comparable efficacy and safety to standard therapy with NPH and RHI injected subcutaneously.[71] Head-to-head trials with insulin analogs have not yet been performed.


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